Capturing variation impact on molecular interactions in the IMEx Consortium mutations data set

The current wealth of genomic variation data identified at nucleotide level presents the challenge of understanding by which mechanisms amino acid variation affects cellular processes. These effects may manifest as distinct phenotypic differences between individuals or result in the development of disease. Physical interactions between molecules are the linking steps underlying most, if not all, cellular processes. Understanding the effects that sequence variation has on a molecule's interactions is a key step towards connecting mechanistic characterization of nonsynonymous variation to phenotype. We present an open access resource created over 14 years by IMEx database curators, featuring 28,000 annotations describing the effect of small sequence changes on physical protein interactions. We describe how this resource was built, the formats in which the data is provided and offer a descriptive analysis of the data set. The data set is publicly available through the IntAct website and is enhanced with every monthly release

Identifying multiscale translational safety biomarkers using a network-based systems approach

Animal testing is the current standard for drug and chemicals safety assessment, but hazards translation to human is uncertain. Human in vitro models can address the species translation but might not replicate in vivo complexity. Herein, we propose a network-based method addressing these translational multiscale problems that derives in vivo liver injury biomarkers applicable to in vitro human early safety screening. We applied weighted correlation network analysis (WGCNA) to a large rat liver transcriptomic dataset to obtain co-regulated gene clusters (modules). We identified modules statistically associated with liver pathologies, including a module enriched for ATF4-regulated genes as associated with the occurrence of hepatocellular single-cell necrosis, and as preserved in human liver in vitro models. Within the module, we identified TRIB3 and MTHFD2 as a novel candidate stress biomarkers, and developed and used BAC-eGFPHepG2 reporters in a compound screening, identifying compounds showing ATF4-dependent stress response and potential early safety signals

Author Correction: COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms (Scientific Data, (2020), 7, 1, (136), 10.1038/s41597-020-0477-8).

An amendment to this paper has been published and can be accessed via a link at the top of the paper

The characterization and development of bioactive hydroxyapatite coatings

Bioactive coatings are currently being plasma-sprayed on implant surfaces in order to optimize bone-implant interactions. However there are problems with the existing coating process, such as poor interfacial adhesion strength, alteration of coating properties, and the lack of an existing coating standard. To overcome some of the problems with the existing plasma-spraying process, investigators are working on other experimental coating methods to increase the adhesion strength as well as to have better control of the coating properties. This review will discuss the advantages and disadvantages of plasma spraying as well as the experimental coating processes

Publisher Correction: Capturing variation impact on molecular interactions in the IMEx Consortium mutations data set (Nature Communications, (2019), 10, 1, (10), 10.1038/s41467-018-07709-6)

10.1038/s41467-019-08814-wNature Communications101109

eTRANSAFE: data science to empower translational safety assessment

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Enhancing osseointegration using surface-modified titanium implants

Osseointegrated dental implants are used to replace missing teeth. The success of implants is due to osseointegration or the direct contact of the implant surface and bone without a fibrous connective tissue interface. This review discusses the enhancement of osseointegration by means of anodized microporous titanium surfaces, functionally macroporous graded titanium coatings, nanoscale titanium surfaces, and different bioactive factors